The regional cerebral metabolic rate for glucose (rCMRglc) was examined in Fischer-344 rats and beagle dogs in relation to age and pharmacological stimulation. In beagles, older than 6 yr. many brain regions showed reduced rCMRglc particularly those involved with sensory function. The brains of the beagles showed no evidence of senile plaques or of neurofibrillary tangles, which characterize Alzheimer's disease in man, nor significant losses of neurons. Oxotremorine, a cholinergi agonist, stimulated rCMRglc in awake rats in brain regions associated with memory function, further supporting a role for acetylcholine in memory. Arecoline, another cholinergic agonist, also stimulated rCMRglc in a number of brain regions, including those with muscarinic receptors. The metabolic responses to arecoline were reduced in senescent as compared to younger rats, suggesting that, there is a defect in cholinergic function in the senescent rat brain. Metabolic responses in awake animals were not influenced by mild immobilization stress. Dopaminergic function in the rat brain was examined by measuring rCMRglc in response to haloperidol (a dopaminergic antagonist), bromocriptine (an agonist) and sulpiride (a specific antagonist). At low drug doses, the responses occurred at dopaminergic receptor sites, whereas at higher doses generalized metabolic involvement occurred. The response to haloperidol was reduced in senescent as compared to younger Fischer-344 rats, despite the fact that higher concentrations of haloperidol accumulated within brains of old rats, suggesting a difference between old and young rats in central dopaminergic function. The metabolic responses to haloperidol were time-dependent and, with long-term treatment, demonstrated tolerance.